VGF

VGF nerve growth factor inducible
Identifiers
Symbol	VGF
Entrez	7425
HUGO	12684
OMIM	602186
RefSeq	NM_003378
UniProt	O15240
Other data
Locus	Chr. 7 q22

VGF or VGF nerve growth factor inducible is a protein and neuropeptide that may play a role in regulating energy homeostasis, metabolism^[1] and synaptic plasticity.^[2] The protein was first discovered in 1985 by Levi et al.^[3] in an experiment with PC12 cells and its name is non-acronymic. VGF gene encodes a precursor which is divided by proteolysis to polypeptides of different mass, which have a variety of functions, the best studied of which is the role of TLQP-21 in the control of appetite and inflammation.^{[4][5][6][7][8][9][10][11]} The expression of VGF and VGF-derived peptides is detected in a subset of neurons in the central and peripheral nervous systems and specific populations of endocrine cells in the adenohypophysis, adrenal medulla, gastrointestinal tract, and pancreas.^[12] VGF expression is induced by NGF, CREB and BDNF and regulated by neurotrophin-3.^[13][14] Physical exercise significantly increases VGF expression in mice hippocampal tissue and upregulates a neurotrophic signaling cascade thought to underlie the action of antidepressants.^{[15][16][17][18]}

Role in pathology

Changes in expression of discrete VGF fragments have been detected in different neurological and psychiatric conditions. In schizophrenia, one study has shown an increase in the VGF23-62 peptide^[19] and a subsequent small study demonstrated that drugs further increase the expression, pointing at a possible ameliorating action of the fragment. A decreased expression of VGF26-62 peptide was found in frontotemporal dementia^[20] and the expression of a fragment containing aminoacids 378-398 was found to be changing in amyotrophic lateral sclerosis^[21] and Alzheimer's disease.^[22] VGF expression has also been shown in damaged peripheral nerves, and it is thought to have a role in neuropathic pain.^[23]

References

1. Hahm S, Mizuno TM, Wu TJ, Wisor JP, Priest CA, Kozak CA, Boozer CN, Peng B, McEvoy RC, Good P, Kelley KA, Takahashi JS, Pintar JE, Roberts JL, Mobbs CV, Salton SR (1999). "Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance". Neuron 23 (3): 537–48. doi:10.1016/S0896-6273(00)80806-5. PMID 10433265.
2. Alder J, Thakker-Varia S, Bangasser DA, Kuroiwa M, Plummer MR, Shors TJ, Black IB (November 2003). "Brain-derived neurotrophic factor-induced gene expression reveals novel actions of VGF in hippocampal synaptic plasticity". Journal of Neuroscience 23 (34): 10800–8. PMC 3374594. PMID 14645472.
3. Levi A, Eldridge JD, Paterson BM (1985). "Molecular cloning of a gene sequence regulated by nerve growth factor". Science 229 (4711): 393–5. doi:10.1126/science.3839317. PMID 3839317.
4. Bartolomucci A, La Corte G, Possenti R, Locatelli V, Rigamonti AE, Torsello A, Bresciani E, Bulgarelli I, Rizzi R, Pavone F, D'Amato FR, Severini C, Mignogna G, Giorgi A, Schininà ME, Elia G, Brancia C, Ferri GL, Conti R, Ciani B, Pascucci T, Dell'Omo G, Muller EE, Levi A, Moles A (September 2006). "TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity". Proceedings of the National Academy of Sciences of the United States of America 103 (39): 14584–9. doi:10.1073/pnas.0606102103. PMC 1600003. PMID 16983076.
5. Rizzi R, Bartolomucci A, Moles A, D'Amato F, Sacerdote P, Levi A, La Corte G, Ciotti MT, Possenti R, Pavone F (August 2008). "The VGF-derived peptide TLQP-21: a new modulatory peptide for inflammatory pain". Neuroscience Letters 441 (1): 129–33. doi:10.1016/j.neulet.2008.06.018. PMID 18586396.
6. Bartolomucci A, Moles A, Levi A, Possenti R (September 2008). "Pathophysiological role of TLQP-21: gastrointestinal and metabolic functions". Eating and Weight Disorders : EWD 13 (3): e49–54. PMID 19011364.
7. Zhao Z, Lange DJ, Ho L, Bonini S, Shao B, Salton SR, Thomas S, Pasinetti GM (2008). "Vgf is a novel biomarker associated with muscle weakness in amyotrophic lateral sclerosis (ALS), with a potential role in disease pathogenesis". International Journal of Medical Sciences 5 (2): 92–9. doi:10.7150/ijms.5.92. PMC 2323610. PMID 18432310.
8. Bartolomucci A, Possenti R, Levi A, Pavone F, Moles A (November 2007). "The role of the vgf gene and VGF-derived peptides in nutrition and metabolism". Genes & Nutrition 2 (2): 169–80. doi:10.1007/s12263-007-0047-0. PMC 2474945. PMID 18850173.
9. D'Amato F, Noli B, Brancia C, Cocco C, Flore G, Collu M, Nicolussi P, Ferri GL (May 2008). "Differential distribution of VGF-derived peptides in the adrenal medulla and evidence for their selective modulation". The Journal of Endocrinology 197 (2): 359–69. doi:10.1677/JOE-07-0346. PMID 18434366.
10. Jethwa PH, Ebling FJ (2008). "Role of VGF-derived peptides in the control of food intake, body weight and reproduction". Neuroendocrinology 88 (2): 80–7. doi:10.1159/000127319. PMID 18408361.
11. Bartolomucci A, Bresciani E, Bulgarelli I, Rigamonti AE, Pascucci T, Levi A, Possenti R, Torsello A, Locatelli V, Muller EE, Moles A (March 2009). "Chronic intracerebroventricular injection of TLQP-21 prevents high fat diet induced weight gain in fast weight-gaining mice". Genes & Nutrition 4 (1): 49–57. doi:10.1007/s12263-009-0110-0. PMC 2654049. PMID 19247701.
12. Levi A, Ferri GL, Watson E, Possenti R, Salton SR (2004). "Processing, distribution, and function of VGF, a neuronal and endocrine peptide precursor". Cell. Mol. Neurobiol. 24 (4): 517–33. doi:10.1023/B:CEMN.0000023627.79947.22. PMID 15233376.
13. Mandolesi G, Gargano S, Pennuto M, Illi B, Molfetta R, Soucek L, Mosca L, Levi A, Jucker R, Nasi S (January 2002). "NGF-dependent and tissue-specific transcription of vgf is regulated by a CREB-p300 and bHLH factor interaction". FEBS Letters 510 (1–2): 50–6. doi:10.1016/S0014-5793(01)03227-6. PMID 11755530.
14. Bozdagi O, Rich E, Tronel S, Sadahiro M, Patterson K, Shapiro ML, Alberini CM, Huntley GW, Salton SR (September 2008). "The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior through a brain-derived neurotrophic factor-dependent mechanism". Journal of Neuroscience 28 (39): 9857–69. doi:10.1523/JNEUROSCI.3145-08.2008. PMC 2820295. PMID 18815270.
15. Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR, Duman RS (2007). "Antidepressant actions of the exercise-regulated gene VGF". Nature Medicine 13 (12): 1476–82. doi:10.1038/nm1669. PMID 18059283.
16. Thakker-Varia S, Krol JJ, Nettleton J, Bilimoria PM, Bangasser DA, Shors TJ, Black IB, Alder J (November 2007). "The neuropeptide VGF produces antidepressant-like behavioral effects and enhances proliferation in the hippocampus". Journal of Neuroscience 27 (45): 12156–67. doi:10.1523/JNEUROSCI.1898-07.2007. PMC 3363962. PMID 17989282.
17. Malberg JE, Monteggia LM (2008). "VGF, a new player in antidepressant action?". Science Signaling 1 (18): pe19–pe19. doi:10.1126/stke.118pe19. PMC 2745068. PMID 18460680.
18. Thakker-Varia S, Alder J (February 2009). "Neuropeptides in depression: role of VGF". Behavioural Brain Research 197 (2): 262–78. doi:10.1016/j.bbr.2008.10.006. PMC 2648305. PMID 18983874.
19. Huang JT, Leweke FM, Oxley D, Wang L, Harris N, Koethe D, Gerth CW, Nolden BM, Gross S, Schreiber D, Reed B, Bahn S (2006). "Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis". PLoS Med. 3 (11): e428. doi:10.1371/journal.pmed.0030428. PMC 1630717. PMID 17090210.
20. Rüetschi U, Zetterberg H, Podust VN, Gottfries J, Li S, Hviid Simonsen A, McGuire J, Karlsson M, Rymo L, Davies H, Minthon L, Blennow K (2005). "Identification of CSF biomarkers for frontotemporal dementia using SELDI-TOF". Exp. Neurol. 196 (2): 273–81. doi:10.1016/j.expneurol.2005.08.002. PMID 16154129.
21. Ranganathan S, Williams E, Ganchev P, Gopalakrishnan V, Lacomis D, Urbinelli L, Newhall K, Cudkowicz ME, Brown RH, Bowser R (2005). "Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis". J. Neurochem. 95 (5): 1461–71. doi:10.1111/j.1471-4159.2005.03478.x. PMC 1540444. PMID 16313519.free full text
22. Carrette O, Demalte I, Scherl A, Yalkinoglu O, Corthals G, Burkhard P, Hochstrasser DF, Sanchez JC (2003). "A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer's disease". Proteomics 3 (8): 1486–94. doi:10.1002/pmic.200300470. PMID 12923774.
23. Moss A, Ingram R, Koch S, Theodorou A, Low L, Baccei M, Hathway GJ, Costigan M, Salton SR, Fitzgerald M (2008). "Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury". Molecular Pain 4: 62. doi:10.1186/1744-8069-4-62. PMC 2614976. PMID 19077191.